文献类型：期刊文献

英文题名：Taming Highly Enolizable Aldehydes via Enzyme Catalysis for Enantiocomplementary Construction of β-Hydroxyphosphonates

作者：Li, Huangong[1];Zhu, Zheng[1];Wu, Dongqi[1];Ju, Yongyuan[1];Li, Dan[1];Zou, Keke[1];Zhu, Chaonan[1];Zhang, Jingyu[1];Zhu, Guoliang[1];Zhang, Lixin[1];Chi, Yonggui Robin[2,3];Xie, Yongtao[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Nanyang Technol Univ, Sch Chem Chem Engn & Biotechnol, Singapore 637371, Singapore;[3]Guizhou Univ, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr Bioengn, Minist Educ, Guiyang 550025, Peoples R China

年份：2025

卷号：147

期号：4

起止页码：3102

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20250417737490);WOS:【SCI-EXPANDED(收录号:WOS:001399588800001)，CCR-EXPANDED(收录号:WOS:001399588800001)】；

基金：The authors acknowledge the National Natural Science Foundation of China (32301231, 32121005), the East China University of Science and Technology for startup funding (YF0142210), the Fundamental Research Funds for the Central Universities (JKF01231815), the National Key Research and Development Program of China (2020YFA0907200, 2020YFA0907800, 2022YFC2303100, and 2022YFC2303104), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, and the 111 Project (B18022).

语种：英文

外文关键词：Catalysis - Enantioselectivity

摘要：Taming highly enolizable aldehydes for catalytic asymmetric C-C coupling with nucleophiles remains an elusive challenge compared to widely explored simple alkyl or aryl aldehydes. Herein, we use ThDP-dependent enzymes to realize the direct C-C coupling of highly enolizable 2-phosphonate aldehydes with in situ-generated dynamically reversible nucleophiles (acyl anions). Unlike NHC-mediated reactions that yield complex mixtures of multiple adducts, our enzymatic process selectively produces biologically active beta-hydroxy phosphonates with high yields (up to 95%) and excellent enantioselectivities (up to 99% ee). The products can be obtained on gram scales and exhibit rich reactivity for downstream transformations to afford diverse molecules. PfBAL (or its mutant A28G) and PaBAL enzymes serve as enantiocomplementary pairs, enabling the synthesis of both product configurations. Mechanistic studies proved that the entrance directions of the active cavities of these two enzyme pairs were distinct, leading to acyl anions formed from these two enzyme pairs attacking 2-phosphonate aldehydes from different orientations.